The impact of fractionation on secondary malignancies in postoperative breast cancer irradiation

Abstract

Purpose: Randomized studies demonstrated the oncological equivalence of (ultra-)hypofractionation compared to a 5-week schedule in postoperative radiotherapy of breast cancer. Due to the low incidence and long latency of secondary malignancies, there are currently no reliable clinical data regarding the influence of fractionation regimens on the development of secondary malignancies. Material and methods: For 20 patients with right or left-sided breast cancer, postoperative treatment plans were created using 3D-CRT (n = 10) or VMAT (n = 10) for three different fractionation schedules: 5-week schedule with 50.4Gy in 1.8Gy (28fx), hypofractionation with 40.05Gy in 2.67Gy (15fx) and ultra-hypofractionation with 26Gy in 5.2Gy (5fx). The EARs (absolute additional cases of disease per 10,000 patient-years) for secondary malignancies in the lung, contralateral breast, esophagus, liver, thyroid, spinal cord, bones and soft tissue were calculated using a fraction-dependent dose-response model. Results: Based on risk modulation, (ultra-)hypofractionation resulted in significantly lower EARs for lung cancer (LC), contralateral breast cancer (CBC) and soft tissue sarcoma (STS) (p < .001). For the ultra-hypofractionated dose concept the median EARs for LC, CBC and STS were 42.8 %, 39.4 % and 58.1 % lower compared to conventional fractionation and 31.2 %, 25.7 % and 20.3 % compared to hypofractionation. The influence of fractionation on the risk of secondary malignancies for LC and CBC was less pronounced with 3D-CRT than with VMAT. For STS, however, the influence of fractionation was greater with 3D-CRT than with VMAT. Conclusion: Based on this simulation study (ultra-)hypofractionated postoperative breast cancer irradiation may be associated with a lower risk of secondary malignancies compared to a 5-week schedule.